Reactivation of murine tumour-infiltrating lymphocytes with solid-phase anti-CD3 antibody: in vitro cytokine production is associated with in vivo efficacy

Simon Goedegebuure, M. Zuber, D. L. Leonard-Vidal, Ú L. Burger, J. C. Cusack, M. P. Chang, L. M. Douville, Timothy Eberlein

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Previously we described the use of solid-phase anti-CD3 monoclonal antibody (mAb) to stimulate murine tumour-infiltrating lymphocytes (TIL) and their subsequent expansion in recombinant interleukin 2 (rlL-2). In a pulmonary metastases model using the methyl-cholanthrene-induced sarcoma MCA-105 anti-CD3 activated TIL were capable of eradicating disease similar to TIL cultured in rIL-2 only. Here we extend these observations by characterizing the biological effects of sequential solid-phase anti-CD3 activation. TIL from MCA-105 tumour activated with solid-phase anti-CD3 on day 1 were reactivated on day 14, or day 26, or both and compared to TIL grown in rIL-2 only or TIL activated with anti-CD3 once on day 1. Reactivation enhanced in vitro proliferation 1.8-to 4-fold compared to TIL activated once with anti-CD3 (P < 0.05). In addition, the total lytic capacity of the cultures was enhanced after reactivation without changing the phenotype of the TIL cultures. Reactivation resulted in a greater in vivo efficacy when the TIL were administered within 72 h of reactivation. In contrast, TIL activated with anti-CD3 on day 1 and day 14 were least effective of all TIL cultures (P < 0.05). This correlated with in vitro cytokine production. The most effective TIL cultures in vivo produced 4- to 100-fold higher amounts of cytokines, especially interferon gamma (IFNγ) and granulocyte macrophage colony stimulating factor (GM-CSF), than the other cultures. On the other hand, the least effective in vivo TIL culture, TIL activated with anti-CD3 on day 1 and 14, produced little or no cytokines. These data suggest that in vitro production of cytokines is indicative of in vivo efficacy of anti-CD3 activated TIL.

Original languageEnglish
Pages (from-to)79-89
Number of pages11
JournalSurgical Oncology
Volume3
Issue number2
DOIs
StatePublished - Apr 1994

Keywords

  • anti-CD3
  • cytokines
  • monoclonal antibody
  • murine
  • reactivation
  • tumour-infiltrating lymphocytes

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